Expression Pattern Of TNFR-1in The Mouse Hair Follicle Cycle And The Preliminary Study Of Its Function

Hair follicle is an important accessory organ in the epidermis,controls the growthof hairs and plays important roles in animal survival.In the entire life of the animal,thehair follicles undergo three different phase periodically,that is,anagen phase,catagenphase and telogen phase,to achieve growth cycle and periodic update of hairs.In anagen,the hair matrix will rapidly and continuously to proliferate and differentiate to form theinner root sheath and hair shaft causing hair follicles grow downward,while some of thehair follicle cells undergo apoptosis so as to avoid excessive cell proliferation.In catagen,hair follicles become shorter due to apotosis of the lower portion,and the dermal papillamoves upward gradually.Dermal papilla moving upward to the area close to bulge,thehair follicle is in telogen.There are various signaling pathways which are Associatedwith the maintenance of hair follicle cycle,and TNF-alpha signaling pathway is one ofthem playing an important role.TNF alpha signal transduction can cause many reactionsin cells such as cell proliferation,differentiation,apoptosis and proinflammation.TNFR-1plays a very important part in TNF-alpha signal transduction as a receptor on the cellmemberane,while its expression pattern in the hair follicle cycle of the postnatal micehas not been studied yet.Objective: To detect the expression profile of TNFR-1in the hair follicles of miceat different phase and explore its importance,to lay a certain foundation for revealing therole which TNFR-1plays in all stages of the hair cycle and transformation betweendifferent stages,to bring inspiration for studying the role of extracellular signalingpathways in the hair follicle and especially to provide the basis for the further study ofTNF alpha signal pathway regulating hair follicle cycle.Methods: RT-PCR,Western blot analysis and immunofluorescence with paraffinsection were adopted to detect the expression and distribution changes of TNFR-1inmouse hair follicles at four time points of P8d,P15d,P18d and P24d separately.Hairshaft differentiation marker AE13and AE15was tested by immunofluorescence.Theapoptosis of the hair follicle was detected by TUNEL staining.Results: The expression intensity of TNFR-1were distinct in all4time points inthe skin.TNFR-1mRNA showed high expression trend from the middle anagen to verylate anagen,and in the catagen and telogen its expression grew lower than that in verylate anagen. From the middle anagen to very late anagen,TNFR-1presented high expression trend. In the catagen and telogen, the expression of TNFR-1was becoming lower than that in very lateanagen and stayed at a very low level. Immunofluorescence showed that in theanagen,TNFR-1was mainly distributed in epidermis, the matrix,the inner root sheath(IRS) and the hair shaft. In the very late anagen phase,there’s significant expression ofTNFR-1in outer root sheath(ORS).In the catagen phase,TNFR-1was distributed inepidermis and ORS,and expressed specifically and highly in the second hair germ.Therewas very low expression of TNFR-1in epidermis and club hair in the telogenphase.AE13was expressed in epidermis,hair cortex and hair cuticle in the anagen.In thecatagen,there was a specific and high expression of AE13in the hair shaft,especially inthe proximal end of the hair shaft,that is,in the area of keratinization and club hairformation.In telogen,there was a low expression of AE13in epidermis and hairclub.AE15was expressed in inner root sheath and medulla in the anagen,and theexpression intensity in the middle anagen become lower than that in the very lateanagen.In the catagen,there was a very low expression of AE15in the remaining innnerroot sheath.In telogen,there was no significant expression of AE13in hairfollicle.Through TUNEL staining,it was found that TUNEL＋cells were detected inepidermis,hair shalft,IRS and hair matrix during anagen.In addition,TUNEL＋cellswere detected in ORS during late anagen.There is TUNEL＋cells in epidermis,ORS andthe proximal end of the hair shaft during catagen.TUNEL＋cells were detected inepidermis,hair club,bulge and sebaceous gland during telogen.Conclusion:TNFR-1is expressed specifically and spatiotemporally in the hairfollicle cycle,and its expression is implicated in Promoting cell differentiation andpro-apoptosis of hair follicle.